When It Comes to Cancer, Just How Vulnerable Are Our Children?
By Mark Lappé
Perhaps the most tragic event in the life of a parent is the death of a child. When
that death is from cancer, parents are often haunted by the belief that it
was something they had done - or not done - that put their child in harm's way.
The reality of course is often much less certain outside our ability to know.
Others are deeply embedded in our genetic legacy.
Many childhood cancers like the special eye cancer called retinoblastoma are
primarily hereditary in origin. In fact, an old adage taught to pathology
students is that if a cancer occurs before adolescence, look to the genes.
But a growing wave of childhood cancers, particularly of the bone marrow and
brain, are likely to have its origins in something else - something in the environment.
As the toxicologist charged with figuring out the "cause" of the
notorious Woburn, Massachusetts cancer cluster (made famous in the film A
Civil Action starring John Travolta as an impassioned attorney, Jan Schlichtman),
I was impressed by two factors. The first was the unshakable conviction of
Anne Anderson, then several of her neighbors ,that there were simply too many
cases of childhood leukemia in their neighborhood to be explained by choice.
Now, epidemiologists are the first to point out the error of seeing cancer
clusters when they are simply random bunches of otherwise rare events, predictable
from the so-called Poisson probability curve. In the Woburn case, it took 10
years before researchers at the Harvard School of Public Health concluded
that the 16 or so childhood cancers found in the small town were probably
not an "accident" at all, and a genuinely clustered event.
The second factor involves the improbable success of the search for a possible
environmental cause: within months after the Woburn Cancer Cluster became
a civil lawsuit under the aegis of Schlichtman's law firm, the toxicology
team found the instinct of the parents to look for contaminated water-bore
fruit. By today's standards, Woburn drinking water was in fact heavily contaminated
by hundreds of parts per billion of two solvents, trichloroethylene and perchloroethylene.
But the lynch pin in the probable cause argument came about in a strange way,
almost all of the parents of the affected children drew their water from two
wells on maps that were separated from the major industrial operation in town,
the Riley Tannery, by the Aberjona river. A brilliant hydrologist connected
the solvents used on the Riley Tannery (a division of Beatrice Foods Company)
to the wells through an underground aquifer that ran under the river by doing
an ingenious"draw-down" test whereby wells on one side of the river
were heavily pumped to see if levels in the distant well on the other side
would fall. They did. A second source of solvent contamination was W.R. Grace
which was even closer to the affected wells.
But from a toxicological view, the most interesting facts were that every
mother who bore a child that subsequently developed leukemia, drank and washed
with water from the two wells throughout their pregnancy. And most compelling,
tests of the immune systems of the affected families and their neighbors - compared
to a suitable group of controls - revealed disturbances in the ability of the
individuals' cells to recognize foreign antigens. This apparent defect may
or may not have been directly caused by the solvent - but the link appeared
inescapable: families with cancer-ridden children were families with sick
My own work had serendipitously prepared me to think about the Woburn case.
As a graduate student in experimental pathology, I had given newborn mice
tiny amounts (about a milligram or 1/1000 gram) of a carcinogen called urethane
within the first day after their delivery. (At this stage, the mice are about
the same developmental stage as a 7-8 month human fetus) The amount of carcinogen,
gave the baby mice even when adjusted for their small body weight would hardly
have been sufficient to cause cancer in an adult animal. I followed the growth
of the tiny animals and their sham-injected littermates through their adulthood.
Along the way, I measured their immune system's strength by giving them skin
grafts of foreign tissue. I then ranked the animals according to their immune
scores. Those with the lowest scores - the ones that took the longest to recognize
and reject the grafts - were ranked against the mice that had the strongest
responses. The low scores of the mice that received carcinogen treatments
(as opposed to the untreated controls) showed that long before any tumors
were visible, the carcinogen had depressed the treated animals immune systems.
Most critically, the mice with the greatest depression had the greatest number
These results suggested three things that other researchers have since confirmed:
that the immune system is important in keeping cancer at bay; that chemicals
that cause cancer can interfere with the normal development of immune strength;
and, that very early exposure to carcinogens can produce dramatic and unexpected
names of cancer in adolescence or young adulthood.
The relevance to the Woburn families was striking, even if only by analogy.
Each of the Woburn residents had been exposed to chemicals that could depress
their immune systems. And each affected child had been exposed during pregnancy
to an intrauterine dose (as well as post natal doses from drinking water)
that could have started the cancer process. . Ironically, virtually no scientists
other than the team put together for the lawsuit saw these connections as
relevant. And the defense, representing Beatrice Foods and W.R. Grace, had
no trouble finding scientists who thought our thinking was ridiculous and
With hindsight, I think the Woburn team was on to something important about
the linkage between young age of exposure and vulnerability to cancer. But
at the time these events transpired, in the mid-1980s, few scientists had
yet formulated their thinking about how to use data about cancer in animals
to predict cancer in humans much less children, a connection currently under
intense review. Only in the last year has the EPA issued draft guidance about
adjusting cancer risk estimates to account for this increased vulnerability
of children to environmental carcinogens.
The Woburn events all transpired before the Environmental Protection Agency
had issued their first Guidelines for Carcinogen Risk Assessment in 1986.
These guidelines put forward procedures and principles for scientists to use
in assessing the public's risk associated with environmental chemicals. In
1996, the EPA published its formal proposal for cancer risk guidelines, and
again in 1999 invited public review of its revised Guidelines.
On March 3, 2003, the EPA published its "Draft Final Guidelines for Carcinogen
Risk Assessment" open for public comment through May 1, 2003. These latest
revisions are designed to incorporate the most recent scientific thinking
about the importance of different mechanisms that might produce cancer, and
in particular invite comments about the importance of understanding and appreciating
"susceptible populations and life stages, in determining cancer risk.
This latter issue is treated separately in an EPA supplemental guidance document
that describes possible approaches for figuring out the risks from early life
exposure to potential carcinogens. The new EPA calculations indicate children
under the age of 2 are 10 times , and children from 2-15 years are three times
more susceptible to chemical carcinogenesis than are adults.
So, twenty years after Woburn, the EPA is finally looking at the possibility
that children-and fetuses-may be especially susceptible to cancer-causing
insults. In fact, an entire neglected field of research called "Perinatal
Carcinogenesis" has now been re-opened. This field was once almost the
exclusive province of Eastern European and Russian researchers. Perhaps surprisingly,
given the resurgence of interest in susceptibility of the fetus, my contemporaries
thought this new field to be too fluid and uncertain to lend itself to scientific
analysis. After all, estimating the actual dose a developing embryo received
from any chemical in its mother's diet or environment was a daunting challenge.
Not only did you have to contend with the questions of trans-placental transfer
of chemicals, but also how much (or little) would first be processed by the
mother's detoxifying system - and then how much would be processed by the still
immature fetus's systems was largely a matter of conjecture. Another key variable
is the high rate of cell division in the developing fetus which puts replicating
cellular DNA at risk for greater genetic damage than the more often quiescent
double-strands in an adult. This factor alone probably explains a considerable
amount of the intra-uterine cancer produced by chemicals exposed via the mother.
Some chemicals, like the notorious diethylstilbestrol (DES), clearly traverse
the placental "barrier" intact, and can cause enough anatomic damage
to lead to cancer in subsequent generations (daughters and sons) of exposed
Whatever the eventual outcome of EPA's belated methods that are finally for assessing
the enhanced childhood and intrauterine risk from environmental carcinogens, we can hope
the resulting warnings about heightened risks during
pregnancy and early life will avert many more tragedies like those that afflicted
the families in Woburn, Massachusetts a quarter of a century ago.